Carbohydrate side-chains are attached to antibody molecules via the dolichol-dependent, asparagine-linked pathway (Granato et al., 1987, Mol. Immunol 24:849-55). In general, one main species of oligosaccharide chain, composed of glucose, mannose and N-acetylglucosamine residues (Glc.sub.3 Man.sub.9 GlcNAc.sub.2) is transferred to the protein moiety of the antibody in the endoplasmic reticulum (ER). The Glc.sub.3 Man.sub.9 GlcNAc.sub.2 precursor oligosaccharide is attached to an NH.sub.2 group on a side chain of an asparagine residue of the protein. The diversity of the carbohydrate side chains results from structural modifications of this single precursor oligosaccharide which begin in the ER and continue during subsequent transit of the nascent glycoprotein through the Golgi apparatus. Indeed, the carbohydrate side chains of the mature antibody molecule result from the activity of a variety of glycosidases that "trim" glucose and mannose residues from the oligosaccharide precursor as well as the activity of other enzymes that add GlcNAc, fucose, galactose and sialic acid residues.
Specific inhibitors which block different enzymes in the trimming process of the biosynthesis of glycoproteins have been known for a number of years (see, e.g., Gross et al., 1983, J. Biol. Chem. 256:12203-09). For instance, 1-deoxynojirimycin has been shown to inhibit glucosidases I and III; swainsonine, to inhibit mannosidase II; and bromoconduritol, to inhibit trimming of the innermost glucose residue of Glc.sub.3 Man.sub.9 GlcNAc.sub.2 (see, Gross et al., supra). Castanospermine has been shown to inhibit some beta-glucosidases (Saul et al., 1983, Arch. Biochem. Biophys. 221:593).